A prospectively randomized, controlled clinical trial comparing adriamycin 60 mg/M2 every three weeks to adriamycin in full dose plus streptozotocin 500 mg/M2 per day times 5 every three weeks has been completed in patients with advanced metastatic soft-tissue and osseous sarcomas. There did not appear to be any difference in rate of remission induction, remission duration or total survival from treatment with this therapy between the two arms. Although toxicity from the drug therapy was tolerable in each arm of the study, it was noted that leukopenia, thrombocytopenia and mucositis were all significantly greater in the patients on the combination drug arm as opposed to the patients receiving adriamycin alone. Pharmacokinetic studies of both adriamycin and streptozotocin plasma clearance in patients treated on both arms showed significantly greater adriamycin drug exposure (concentration X time) in patients who were receiving adriamycin with streptozotocin compared with patients receiving adriamycin only. The terminal excretory half-life of adriamycin plasma fluorescence was also prolonged. On the other hand, streptozotocin clearance appeared similar to that of patients who were receiving streptozotocin only. Overall, the evidence from the clinical and pharmacokinetic studies implies that streptozotocin-induced hepatotoxicity, while of itself mild and self-limited, impairs the hepatic metabolism and/or excretion of adriamycin in a clinically significant fashion in man.